Membrane type-1 matrix metalloproteinase promotes human melanoma invasion and growth
| Autor: | Leo T. Furcht, James B. McCarthy, Joji Iida, Krista L. Wilhelmson, Duanqing Pei, Matthew Price, Christopher M. Wilson |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Pathology
Skin Neoplasms Fibrosarcoma Biocompatible Materials Matrix metalloproteinase Biochemistry Extracellular matrix Mice 0302 clinical medicine Laminin Mice Inbred NOD Melanoma 0303 health sciences Metalloproteinase Enzyme Precursors biology Metalloendopeptidases invasion Drug Combinations Gelatinases 030220 oncology & carcinogenesis embryonic structures Female Proteoglycans Collagen Cell Division musculoskeletal diseases Collagen Type IV medicine.medical_specialty Injections Intradermal Matrix Metalloproteinases Membrane-Associated growth macromolecular substances Dermatology Transfection Collagen Type I 03 medical and health sciences stomatognathic system Cell Line Tumor medicine Matrix Metalloproteinase 14 Animals Humans Neoplasm Invasiveness Molecular Biology 030304 developmental biology Matrigel Cell Biology medicine.disease Tumor progression Cell culture biology.protein Cancer research Neoplasm Transplantation |
| Zdroj: | The Journal of investigative dermatology. 122(1) |
| ISSN: | 0022-202X |
| Popis: | Membrane type-I metalloproteinase (MT1-MMP) is a transmembrane metalloproteinase that is critical for tumor cell invasion. MT1-MMP can degrade extracellular matrix (ECM) proteins directly and/or indirectly by activating soluble MMPs such as pro-MMP-2. Although MT1-MMP is upregulated in malignant melanoma, the biological consequences of elevated MT1-MMP expression for tumor progression are not entirely understood. In the current study, we have utilized the Bowes melanoma line for evaluating MT1-MMP in invasion and growth. Our studies extend the earlier observations to demonstrate that MT1-MMP expression in Bowes melanoma cells promotes selective invasion into matrigel but not matrices consisting of type-I collagen. Furthermore, MT1-MMP expressing melanoma cells exhibit increased migration in response to laminin 1 but not to type-I or type-IV collagen. MT1-MMP expression results in enhanced 3 dimensional growth in agarose gels and in long-term cultures within matrigel. The hydroxymate inhibitor BB94 inhibits MT1-MMP enhanced invasion and growth in 3 dimensional culture systems, but had no effect on increased motility. We demonstrated that MT1-MMP expression significantly facilitated tumorigenicity and growth by intradermal injection. The results suggest a more general role for elevated MT1-MMP in promoting both the selective invasion and increased growth of malignant melanoma in vivo. |
| Databáze: | OpenAIRE |
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